Psoriasis is an inflammatory skin condition whose cause is unknown. The condition involves thick scaling due to epidermal cell proliferation, cracking and bleeding. Mast cells have recently noted as being involved in psoriasis.
Inflammation is a non-specific response of tissues to diverse stimuli or insults and results in release of a variety of materials at the site of inflammation that induce pain. It is now recognized that mast cells, neutrophils and T-cells are implicated in the pathophysiology of inflammatory skin conditions as well as in other physiological disorders. Mast cells provide the greatest source of histamines in acute inflammation, as well as chymases, after degranulation by IgE.
Neutrophils are prominent in psoriatic lesions due to the potent chemoattractants released by mast cells.
Neutrophils are a main source of serine elastase and cathepsin G which are important in the tissue damage of inflammation.
The most direct approach to therapy of psoriasis skin appears to be a direct attack at the site of inflammation of the mediators of inflammation and pain and the reduction of those neutrophilic derivatives which can cause damage to the growth of new tissue during the healing process.
Disodium cromoglycate has been shown to inhibit the immediate and late-phase inflammatory reactions effectively by decreasing mast cell degranulation. Corticosteroids prevent late-phase inflammatory reactions partly by diminishing the neutrophilic infiltration triggered by mast cell degranulation. Serine protease inhibitors such as .alpha..sub.1 -antitrypsin and .alpha..sub.1 -antichymotrypsin have been found to be useful in the treatment of atopic dermatitis by inhibiting and/or binding with elastase, cathepsin G and human mast cell chymase. However, each of the prior art methods of treatment for psoriases has involved long periods of treatment without success in its long term management. It is recognized that prolong treatment with steroids can cause many side effects. Yet when a psoriasis patient is removed from steroids there is almost immediate relapse to the prior condition.
Alpha 1-antichymotrypsin is a plasma protease inhibitor synthesized in the liver. It is a single glycopeptide chain of approximately 68,000 daltons and belongs to a class of serine protease inhibitors with an apparent affinity toward chymotrypsin-like enzymes. Alpha 1-antichymotrypsin is structurally related to alpha 1-antitrypsin.
Alpha 2-macroglobulin is a glycoprotein containing 8-11% carbohydrate which can be isolated from plasma by gel filtration chromatography.
Alpha 1-proteinase inhibitor (alpha 1-antitrypsin) is a glycoprotein having a molecular weight of 53,000 determined by sedimentation equilibrium centrifugation. The glycoprotein consists of a single polypeptide chain to which several oligosaccharide units are covalently bonded. Human alpha 1-proteinase inhibitor has a role in controlling tissue destruction by endogenous serine proteinases. A genetic deficiency of alpha-1-proteinase inhibitor, which accounts for 90% of the trypsin inhibitory capacity in blood plasma, has been shown to be associated with the development of asthma and pulmonary emphysema. The degradation of elastin associated with certain inflammatory diseases probably results from a local imbalance of elastolytic enzymes and the naturally occurring tissue and plasma proteinase inhibitors. Alpha-1-proteinase inhibitor inhibits human pancreatic and leukocyte elastases. See Pannell et al, Biochemistry. 13, 5339 (1974); Johnson et al, Biochem. Biophys. Res. Commun., 72 33 (1976); Del Mar et al, Biochem. Biophys. Res. Commun., 88, 346 (1979); and Heimburger et al, Proc. Int. Res. Conf. Proteinase Inhibitors. 1st, 1-21 (1970).
The article of Groutas entitled "Inhibitors of Leukocyte Elastase and Leukocyte Cathepsin G Agents for the Treatment of Emphysema and Related Ailments" Medical Research Reviews, Vol. 7, No. 7, 227-241 (1987), discloses the role of eglin, elastinal 1 and elastin in emphysema.
Lezdey et al U.S. Pat. No. 4,916,117 discloses the treatment of pulmonary inflammation where mast cells are involved with microcrystalline alpha-1-antichymotrypsin alone or with other serine protease inhibitors.